We propose to study pediatric myelodysplastic syndromes (MDS), which are blood cancers characterized by ineffective hematopoiesis. MDS has a much higher incidence in adults, but there is an urgent need for a pediatric approach to diagnosis and treatment: the presentation and clinical course is much more heterogeneous and the disease etiology has not been well studied. Prognosis is poor as progression to advanced disease and leukemia can occur rapidly. Transplantation is the only cure, although treatment failure due to procedure-related mortality and disease recurrence can occur. Alternative therapies are available for adult patients ineligible for transplant, but little study has been don in children. Development of new effective therapies for pediatric MDS requires a better understanding of unique and common hematologic features, which could provide important insights into mechanisms that underlie disease and drive progression. We have obtained 129 pediatric and 100 adult patient samples, along with demographic and MDS pathology details, from the National Marrow Donor Program (NMDP) and Center for International Blood and Marrow Transplant Research (CIBMTR). Further, we have obtained age-matched PBMC controls from 20 adult normal donors and are currently obtaining PBMC from 20 pediatric normal donors. We will: 1) evaluate cells using FACS analysis and established characterization panels including T cell, B cell, natural killer t (NKT) cell and natural killer (NK) cell populatios, monocyte subsets, circulating CD34+ cells, and immune-regulatory populations (e.g., T regulatory cells and myeloid derived suppressor cells); 2) examine lymphocyte and immune-regulatory function in subsets including proliferation, cytokine and chemokine production, degranulation and cytotoxicity. For immune-regulatory populations, measure ability to suppress function performing co-culture assays; and 3) Evaluate clinical correlations (e.g., age, disease status, karyotype, transplant outcome and cytomegalovirus sero-status) with pediatric MDS PBMC phenotypic and functional characteristics and compare to adult MDS patients. Our goal is to comprehensively evaluate and compare pediatric and adult MDS with regard to cell type, function, etc. This work is an important step toward better understanding pediatric MDS biology and developing new treatment strategies.